A5003595548- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Nerve injury and regeneration
- Autophagy in Disease and Therapy
- Zebrafish Biomedical Research Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological diseases and metabolism
- Nuclear Receptors and Signaling
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- Pluripotent Stem Cells Research
- Spinal Cord Injury Research
- Autism Spectrum Disorder Research
- Conducting polymers and applications
- Retinal Development and Disorders
- Botulinum Toxin and Related Neurological Disorders
- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Cannabis and Cannabinoid Research
- Neurotransmitter Receptor Influence on Behavior
The Ohio State University Wexner Medical Center
2024
Neurological Surgery
2021-2024
The Ohio State University
2021-2024
University of Pittsburgh
2008-2023
Institute for Neurodegenerative Disorders
2007-2023
Recent studies delineate a pathway involving familial Parkinson's disease (PD)-related proteins PINK1 and Parkin, in which PINK1-dependent mitochondrial accumulation of Parkin targets depolarized mitochondria towards degradation through mitophagy. The has been primarily characterized cells less dependent on for energy production than neurons. Here we report that neurons, unlike other cells, depolarization by carbonyl cyanide m-chlorophenyl hydrazone did not induce translocation to or...
Abstract Individuals with Parkinson’s disease (PD) typically receive a diagnosis once they have developed motor symptoms, at which point there is already significant loss of substantia nigra dopamine neurons, α-synuclein accumulation in surviving and neuroinflammation. Consequently, the clinical presentation may be too late to initiate disease-modifying therapy. In contrast this reality, animal models often involve acute neurodegeneration potential therapies are tested concurrently or...
Dysregulation of mitochondrial biogenesis is implicated in the pathogenesis neurodegenerative diseases such as Parkinson9s disease (PD). However, it not clear how regulated neurons, with their unique compartmentalized anatomy and energetic demands. This particularly relevant PD because selectively vulnerable neurons feature long, highly arborized axons where degeneration initiates. We previously found that exposure to chronic, sublethal doses rotenone, a complex I inhibitor linked PD, causes...
In Parkinson's disease, oxidative stress is implicated in protein misfolding and aggregation, which may activate the unfolded response by endoplasmic reticulum (ER). Dopamine (DA) can initiate via H(2)O(2) formation DA metabolism oxidation into quinone. We have previously shown that quinone induces modification, mitochondrial dysfunction vitro, dopaminergic cell toxicity vivo vitro. this study, we used cysteine- lysine-reactive fluorescent dyes with 2D difference in-gel electrophoresis, mass...
Convergent evidence implicates impaired mitochondrial function and α-Synuclein accumulation as critical upstream events in the pathogenesis of Parkinson's disease, but comparatively little is known about how these factors interact to provoke neurodegeneration. We previously showed that knockdown protected rat substantia nigra dopaminergic neurons from systemic exposure complex I inhibitor rotenone. Here we show motor abnormalities prior neuronal loss this model are associated with extensive...
Abstract A repeat expansion mutation in the C9orf72 gene is leading known genetic cause of FTD and ALS. The C9orf72- ALS/FTD field has been plagued by a lack reliable tools to monitor this genomic locus its RNA protein products. We have validated assays that quantify pathobiology at DNA, levels using knock-out human iPSC lines as controls. Here we show single-molecule sequencing can accurately measure faithfully report on changes what traditionally hard sequence region. This particular value...
Abstract Objective Gene therapy by convection‐enhanced delivery of type 2 adeno‐associated virus‐glial cell derived neurotrophic factor (AAV2‐GDNF) to the bilateral putamina seeks increase GDNF gene expression and treat Parkinson's disease (PD). Methods A 63‐year‐old man with advanced PD received AAV2‐ in a clinical trial. He died from pneumonia after anterior cervical discectomy fusion 45 months later. An autopsy included brain examination for transgene expression. Putaminal catecholamine...
Optogenetic approaches in transparent zebrafish models have provided numerous insights into vertebrate neurobiology. The purpose of this study was to develop methods activate light-sensitive transgene products simultaneously throughout an entire larval zebrafish.